Description
Moxifloxacin-Canon Pharmacodynamics
Moxifloxacin is a bactericidal, broad-spectrum antibacterial drug of the fluoroquinolone series. Bactericidal effect of the drug is due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of replication, repair and transcription of DNA biosynthesis of the microbial cell and, consequently, to the death of microbial cells.
Minimum bactericidal concentrations of moxifloxacin are generally comparable to its minimal inhibitory concentrations.
The mechanisms leading to the development of resistance to penicillins, cephalreporins, aminoglycosides, macrolides and tetracyclines do not impair the antibacterial activity of moxifloxacin. Cross-resistance between these groups of antibacterial agents and moxifloxacin has not been observed. No cases of plasmid resistance have been observed so far either. The overall incidence of resistance is very low (10’7 – Yu’10). Resistance to moxifloxacin develops slowly through multiple mutations. Repeated exposure of microorganisms to moxifloxacin in concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase in the MIC. There are cases of cross-resistance to quinolones. Nevertheless, some resistant to other quinolones Gram-positive and anaerobic microorganisms retain sensitivity to moxifloxacin. It was found that the addition of methoxy group in C8 position in the structure of moxifloxacin molecule increases the activity of moxifloxacin and reduces the formation of resistant mutant strains of Gram-positive bacteria. The addition of the bicycloamino group at the C7 position prevents the development of active efflux (mechanism of resistance to fluoroquinolones).
Moxifloxacin in vitro is active against a wide range of Gram-negative and Gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical bacteria such as Mycoplasma spp., Chlamydia spp., Legionella spp. as well as bacteria resistant to p-lactams and macrolide antibiotics.
In two studies conducted on volunteers, the following changes in the intestinal microflora after oral administration of moxifloxacin were noted. There was a decrease in concentrations of Escherichia coli, Bacillus spp., Bacteroides vulgatus, Enterococcus spp., Klebsiella spp. as well as anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within two weeks. Clostridium difficile toxin was not detected.
Indications
Infectious and inflammatory diseases caused by microorganisms sensitive to moxifloxacin:
– Acute sinusitis.
– Community-acquired pneumonia, including community-acquired pneumonia caused by strains of microorganisms with multiple antimicrobial resistance
– Exacerbation of chronic bronchitis
– Uncomplicated skin and soft tissue infections
– Complicated skin and soft tissue infections (including infected diabetic foot)
– Complicated intra-abdominal infections, including polymicrobial infections, including intraperitoneal abscesses.
– Uncomplicated pelvic inflammatory diseases (including salpingitis and endometritis)
Streptococcus pneumoniae with multi-resistance, including penicillin-resistant strains, strains resistant to 2 or more antibacterials from groups such as penicillins (at MIC ≥ 2 µg/ml), second-generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim/sulfamethoxazole. Current official guidelines on the use of antibacterials must be taken into consideration.
Contraindications
– Hypersensitivity to moxifloxacin, other quinolone-type drugs and any other component of the drug.
– Age under 18 years.
– Pregnancy and breast-feeding period.
– Lesion of the tendon from the previous treatment with quinolones.
– Hereditary lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
– In preclinical and clinical studies after moxifloxacin administration it was observed changes in electrophysiological parameters of the heart, manifested in prolongation of the QT interval. Due to this fact, the use of moxifloxacin is contraindicated in patients with the following categories: congenital or acquired documented prolongation of the QT interval, electrolyte disorders, especially unadjusted hypokalemia, clinically significant bradycardia, clinically significant heart failure with reduced left ventricular ejection fraction and history of rhythm disturbances with clinical symptomatology;
– Moxifloxacin should not be used with other drugs that prolong the QT interval;
– Due to the limited amount of clinical data the use of moxifloxacin is contraindicated in patients with hepatic impairment (class C according to Child-Pugh classification) and patients with transaminases elevated more than five times the upper limit of normal.
How to use and dosages.
- Orally.
- Recommended dosage regimen: One tablet (400 mg) 1 time per day for any infections listed above. Do not exceed the recommended dosage.
- Orally, swallow it whole; do not chew the tablets.
- Duration of therapy. The duration of treatment is determined by the localization and severity of the infection, as well as by the clinical effect.
– Exacerbation of chronic bronchitis – 5-10 days.
– Community-acquired pneumonia: total duration of step therapy (intravenous injection followed by oral administration) – 7-14 days.
– Acute sinusitis – 7 days.
– Uncomplicated skin and soft tissue infections – 7 days.
– Complicated infections of the skin and soft tissues: total duration of step therapy (intravenous injection followed by ingestion) – 7-21 days.
– Complicated intra-abdominal infections: total duration of step therapy (intravenous injection followed by ingestion) – 5-14 days.
– Uncomplicated inflammatory diseases of the pelvic organs – 14 days. - Do not exceed the recommended duration of treatment.
The duration of treatment with moxifloxacin can reach 21 days. - Elderly patients
There is no need to change the dosage regimen in elderly patients. - Children.
Efficacy and safety of moxifloxacin in children and adolescents has not been established. - Liver dysfunction (class A and B according to the Child-Pugh classification).
Patients with liver dysfunction do not need to change the dosage regimen (for the use of the drug in patients with cirrhosis, see section “Cautions”). - Renal failure.
In patients with impaired renal function (including renal failure with creatinine clearance <30 ml/min/1.73 sq.m) and in patients on continuous hemodialysis and long-term ambulatory peritoneal dialysis it is not required a dosage change. - Use in patients of different ethnic groups.
No change in dosing regimen is required.
